Phase I. In the treatment of cancer, radiation therapy has been limited by the tolerance of the surrounding normal tissues, such as lung or mucosa. Until now, there have been no compounds available that protect the normal tissues without reducing the tumor response to radiation therapy. The overall goal of this project is to develop a new approach to radiation therapy for cancer, based on the recently discovered radioprotective effects of novel synthetic catalytic SOD mimetic compounds. These compounds may also independently inhibit tumor growth under certain conditions. In Phase 1 of this SBIR application specific SOD mimetics will have demonstrated effectiveness in animal models of radiation therapy of human cancers. The proposed study will specifically research a selected compound in preparation for human studies directed at enhancing the efficacy of radiation therapy. The goal is to both increase tolerance of normal tissues to radiation therapy and retain or increase the net anti-tumor effects. Well-established functional, radiographic and histopathologic end-points will be used to assess possible mechanisms behind this compound's radioprotective effect in rat and hamster models of radiation-induced injury. Models of both radiation-induced mucositis and radiation-induced lung fibrosis will be studied. The antitumor effect of the selected SOD mimetic given alone or in combination with radiation therapy will be evaluated by using standard tumor growth delay assays. This new strategy of utilizing a single compound with both anti-tumor and radioprotective properties in combination with radiotherapy could result in an improvement in patient survival with a concomitant reduction in the risk of complications. The potential of independent tumor growth inhibition by the SOD mimetics would be an additional benefit.